Biological Impact of a Large Scale Genomic Inversion that Grossly Disrupts the Relative Positions of the Origin and Terminus Loci of the Streptococcus pyogenes Chromosome

Abstract

ABSTRACTA large-scale genomic inversion encompassing 0.79 Mb of the 1.816 Mb-longStreptococcus pyogenesserotype M49 strain NZ131 chromosome spontaneously occurs in a minor subpopulation of cells, and in this report genetic selection was used to obtain a stable lineage with this chromosomal rearrangement. This inversion, which drastically displaces theorisite, changes the relative length of the replication arms so that one replichore is approximately 0.41 Mb while the other is about 1.40 Mb in length. Genomic reversion to the original chromosome constellation is not observed in PCR-monitored analyses after 180 generations of growth in rich medium. As compared to the parental strain, the inversion surprisingly demonstrates a nearly identical growth pattern in exponential phase. Similarly, when cultured separately in rich medium during prolong stationary phase or in an experimental acute infection animal model (Galleria mellonella), the survival rate of both the parental strain and the invertant is equivalent. However, when co-incubated together, both in vitro and in vivo, the survival of the invertant declines relative to the parental strain. The accompanying aspect of the study suggests that inversions taking place nearbyoriC, always happen to secure the linkage oforiC to DNA sequences responsible for chromosome partition. The biological relevance of large scale inversions is also discussed.IMPORTANCEBased on our previous work, we created to our knowledge the largest asymmetric inversion covering 43.5% of theS. pyogenesgenome. In spite of a drastic replacement of origin of replication and the unbalanced size of replichores (1.4 Mb vs 0.41 Mb), the invertant, when not challenged with its progenitor, showed impressive vitality for growthin vitroand pathogenesis assays. The mutant supports the existing idea that slightly deleterious mutations can provide the setting for secondary adaptive changes. Furthermore, comparative analysis of the mutant with previously published data strongly indicate that even large genomic rearrangements survive provided that the integrity of theoriC and the chromosome partition cluster is preserved.